- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03728426
Letermovir Treatment for Refractory or Resistant Cytomegalovirus Infection
A Phase 2 Study of Letermovir Treatment for Patients Experiencing Refractory or Resistant Cytomegalovirus Infection or Disease With Concurrent Organ Dysfunction
Study Overview
Detailed Description
This is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved letermovir for treatment of cytomegalovirus infection, but it has approved letermovir for the prevention of cytomegalovirus infection in bone-marrow transplantation patients.
This is the first time that letermovir will be administered to children in a clinical trial.
Cytomegalovirus (CMV) is a common virus, which a majority of people acquire at some time in their life. CMV remains in your body, but does not cause symptoms in the majority of people. Patients with a weakened immune system (a system that protects you from infections) may be more at risk for the virus becoming active and causing damage to some of your organs, especially in the gut and lungs. If the virus becomes present above a certain quantity, the doctor usually prescribes a drug to treat the infection at this stage to avoid damage to the organs.
In this case, the virus is no longer responding to the prescribed drug, and other drug options will be harmful to the participant's health. Participants are being invited to take part in a research study for an investigational drug called letermovir. The purpose of this study is to find out whether letermovir is as effective and as safe in treating CMV infection in patients who cannot tolerate standard treatments such as ganciclovir or foscarnet.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, United States, 02214
- Massachusetts General Hospital Cancer Center
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Boston, Massachusetts, United States, 02215
- Boston Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥12 years
- Weight ≥30 kg
- Transplant recipient (HCT, SOT) or other immunocompromised patients including those with HIV infection that require antiviral treatment for CMV.
- Documented CMV disease or persistent CMV infection (CMV virus load above 500 IU/mL on consecutive measurements, at least one day apart).
- CMV infection is refractory to treatment (defined as ≥14 days of standard CMV treatment without clinical improvement for CMV disease, or failure to achieve >1 log reduction in CMV VL after ≥14 days of standard treatment for CMV infection)16,17
- Current CMV infection has documented genotypic resistance to ganciclovir or foscarnet.
- For patients with any prior CMV infection episode that broke through letermovir prophylaxis, but not during the current CMV infection, documentation of letermovir susceptibility testing should demonstrate absence of letermovir mutations known to confer resistance to letermovir.
Severe myelosuppression (ANC <1000/µL, Hemoglobin <8g/dL, or Platelets <25,000/µL)17 or renal dysfunction (estimated creatinine clearance <60 mL/min by MDRD in adults or < 60 ml/min/1.73 m2 by bedside Schwartz equation in < 18 years-old) at baseline or which develops during antiviral treatment.
--Patients who develop severe myelosuppression or renal dysfunction during antiviral treatment as defined above are eligible without having to meet the refractoriness/antiviral resistance criterion.
- Combinations of genotypic antiviral resistance and organ dysfunction that lead to eligibility are presented in the full protocol eligibility table.
The effects of letermovir on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of letermovir administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of letermovir administration.
--Patients of childbearing potential must have a negative serum or urine pregnancy test.
- Able to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to letermovir.
- Known history of cirrhosis with Child-Pugh Class C hepatic insufficiency at screening.
- Acute liver injury at baseline meeting Hy's law.
- Current CMV infection broke through letermovir prophylaxis.
- Patients with life expectancy of less than a week. Determination of life expectancy will be discussed with the patient's primary treatment physician.
- Patient taking strong inhibitors or inducers of hepatic CYP enzymes including rifampicin, phenytoin, clarithromycin, ritonavir, or cobicistat.
- HIV patients who are receiving antiretroviral treatment protease inhibitors (darunavir, lopinavir, etc) whether by themselves or boosted with ritonavir or cobicistat, or HIV patients receiving cyclosporine treatment due to strong drug-drug interactions.
- Combinations of genotypic antiviral resistance and organ dysfunction that do not meet eligibility criteria are described in the full protocol eligibility table.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Letermovir
Open label letermovir will be administered daily for up to 12 weeks.
The study allows an optional additional 12 weeks of treatment for secondary prophylaxis if clinically indicated.
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Patients will receive intravenous or oral letermovir at a dose of 480mg/day. Patients weighing 40 or more kilograms will receive a second, loading, dose 12 hours after the first dose of letermovir treatment. For patients receiving concomitant cyclosporine treatment, the letermovir dose will be 240mg/day.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Virological response on treatment Week 6
Time Frame: 6 weeks
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A ≥2 log decrease in plasma CMV DNA from baseline, or an undetectable CMV DNA, measured on treatment week 6. For patients with CMV disease, improvement or resolution of clinical disease by week 6 (i.e., improvement in signs and symptoms of affected organs [resolution of diarrhea, pneumonia, hepatitis, retinitis, etc.]) |
6 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 6 months
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number of patients alive
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6 months
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CMV progression-free survival
Time Frame: 6 months
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Time from study enrollment to CMV progression or death whichever occurs first
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6 months
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Kinetics of viral clearance and potential emergence of letermovir-resistant CMV virus in patients treated in this setting
Time Frame: 6 months
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time to undetectable plasma CMV DN and time to breakthrough infection in patients receiving letermovir treatment who experience an initial virological response.
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6 months
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Proportion of patients with a clinically meaningful treatment response to letermovir treatment
Time Frame: 6 Weeks
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Virological response and a concomitant clinical response in patients with CMV disease by Week 6 of treatment.
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6 Weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Amy C Sherman, MD, Dana-Farber Cancer Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Virus Diseases
- Disease Attributes
- DNA Virus Infections
- Herpesviridae Infections
- Infections
- Communicable Diseases
- Cytomegalovirus Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Poly(ADP-ribose) Polymerase Inhibitors
- Letermovir
Other Study ID Numbers
- 18-348
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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